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Firsov, Alexander A., Elena N. Strukova, Darya S. Shlykova, Yury A. Portnoy, Varvara K. Kozyreva, Mikhail V. Edelstein, Svetlana A. Dovzhenko, Mikhail B. Kobrin, and Stephen H. Zinner. "Bacterial Resistance Studies UsingIn VitroDynamic Models: the Predictive Power of the Mutant Prevention and Minimum Inhibitory Antibiotic Concentrations." Antimicrobial Agents and Chemotherapy 57, no. 10 (July 29, 2013): 4956–62. http://dx.doi.org/10.1128/aac.00578-13.
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ABSTRACTIn light of the concept of the mutant selection window, i.e., the range between the MIC and the mutant prevention concentration (MPC), MPC-related pharmacokinetic indices should be more predictive of bacterial resistance than the respective MIC-related indices. However, experimental evidence of this hypothesis remains limited and contradictory. To examine the predictive power of the ratios of the area under the curve (AUC24) to the MPC and the MIC, the selection of ciprofloxacin-resistant mutants of fourEscherichia colistrains with different MPC/MIC ratios was studied. Each organism was exposed to twice-daily ciprofloxacin for 3 days at AUC24/MIC ratios that provide peak antibiotic concentrations close to the MIC, between the MIC and the MPC, and above the MPC. ResistantE. coliwas intensively enriched at AUC24/MPCs from 1 to 10 h (AUC24/MIC from 60 to 360 h) but not at the lower or higher AUC24/MPC and AUC24/MIC ratios. AUC24/MPC and AUC24/MIC relationships of the areas under the time courses of ciprofloxacin-resistantE. coli(AUBCM) were bell-shaped. A Gaussian-like function fits the AUBCM-AUC24/MPC and AUBCM-AUC24/MIC data combined for all organisms (r2= 0.69 and 0.86, respectively). The predicted anti-mutant AUC24/MPC ratio was 58 ± 35 h, and the respective AUC24/MIC ratio was 1,080 ± 416 h. Although AUC24/MPC was less predictive of strain-independentE. coliresistance than AUC24/MIC, the established anti-mutant AUC24/MPC ratio was closer to values reported forStaphylococcus aureus(60 to 69 h) than the respective AUC24/MIC ratio (1,080 versus 200 to 240 h). This implies that AUC24/MPC might be a better interspecies predictor of bacterial resistance than AUC24/MIC.
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Strukova, Elena N., Yury A. Portnoy, Andrey V. Romanov, Mikhail V. Edelstein, Stephen H. Zinner, and Alexander A. Firsov. "Searching for the Optimal Predictor of Ciprofloxacin Resistance in Klebsiella pneumoniae by UsingIn VitroDynamic Models." Antimicrobial Agents and Chemotherapy 60, no. 3 (December 7, 2015): 1208–15. http://dx.doi.org/10.1128/aac.02334-15.
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There is growing evidence of applicability of the hypothesis of the mutant selection window (MSW), i.e., the range between the MIC and the mutant prevention concentration (MPC), within which the enrichment of resistant mutants is most probable. However, it is not clear if MPC-based pharmacokinetic variables are preferable to the respective MIC-based variables as interstrain predictors of resistance. To examine the predictive power of the ratios of the area under the curve (AUC24) to the MPC and to the MIC, the selection of ciprofloxacin-resistant mutants of threeKlebsiella pneumoniaestrains with different MPC/MIC ratios was studied. Each organism was exposed to twice-daily ciprofloxacin for 3 days at AUC24/MIC ratios that provide peak antibiotic concentrations close to the MIC, between the MIC and the MPC, and above the MPC. ResistantK. pneumoniaemutants were intensively enriched at an AUC24/MIC ratio of 60 to 360 h (AUC24/MPC ratio from 2.5 to 15 h) but not at the lower or higher AUC24/MIC and AUC24/MPC ratios, in accordance with the MSW hypothesis. AUC24/MPC and AUC24/MIC relationships with areas under the time courses of ciprofloxacin-resistantK. pneumoniae(AUBCM) were bell shaped. These relationships predict highly variable “antimutant” AUC24/MPC ratios (20 to 290 h) compared to AUC24/MIC ratios (1,310 to 2,610 h). These findings suggest that the potential of the AUC24/MPC ratio as an interstrain predictor ofK. pneumoniaeresistance is lower than that of the AUC24/MIC ratio.
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Palupi, Maria Fatima, Eli Nugraha, Meutia Hayati, and Neneng Atikah. "Mutant Prevention Concentration Siprofloksasin Terhadap Escherichia coli Patogen dari Kloaka Broiler Secara In Vitro." Jurnal Sain Veteriner 39, no. 1 (April 1, 2021): 20. http://dx.doi.org/10.22146/jsv.57040.
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Mutant prevention concentration (MPC) is an in vitro test used to determine the lowest drug concentration needed to inhibit the growth of a single-step-mutant bacterial subpopulation. The purpose of this study was to determine the MPC value of ciprofloxacin against pathogenic Escherichia coli to obtained the range of mutant selection windows (MSW) of ciprofloxacin. Ciprofloxacin is a quinolone group that is included in the Highest Priority Critically Important Antimicrobials for Human Medicine but is also used for the treatment of bacterial infections in production animals. Twenty-four of pathogenic E. coli isolates sensitive to ciprofloxacin were tested to obtain MPC values and minimum inhibitory concentration (MIC) values. Test the MPC and MIC values to get the MSW range is done by the method of agar dilution. Mueller-Hinton agar containing standard ciprofloxacin was inoculated with 1010 cfu E. coli for the MPC test and 104 for the MIC test. Based on the MPC test results, the MPC value of ciprofloxacin was 4-64 μg / mL (22.96 ± 19.07 μg / mL) and there was one isolate which had an MPC> 256 μg / mL. These results give a wide range of MSW with a lower limit of the MIC value of 0.25 - 2 µg / mL (0.55 ± 0.37 µg / mL) to the upper limit of the MPC value of 4-64 µg / mL (22.96 ± 19.07 μg / mL). Based on the results of this MPC assessment it can be concluded that the dose of ciprofloxacin in production animals has a wide range of MSW that is allow for single-step mutants.
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Firsov, Alexander A., Maria V. Golikova, Elena N. Strukova, Yury A. Portnoy, Andrey V. Romanov, Mikhail V. Edelstein, and Stephen H. Zinner. "In VitroResistance Studies with Bacteria That Exhibit Low Mutation Frequencies: Prediction of “Antimutant” Linezolid Concentrations Using a Mixed Inoculum Containing both Susceptible and Resistant Staphylococcus aureus." Antimicrobial Agents and Chemotherapy 59, no. 2 (December 1, 2014): 1014–19. http://dx.doi.org/10.1128/aac.04214-14.
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ABSTRACTBacterial resistance studies usingin vitrodynamic models are highly dependent on the starting inoculum that might or might not contain spontaneously resistant mutants (RMs). To delineate concentration-resistance relationships with linezolid-exposedStaphylococcus aureus, a mixed inoculum containing both susceptible cells and RMs was used. An RM selected after the 9th passage of the parent strain (MIC, 2 μg/ml) on antibiotic-containing media (RM9; MIC, 8 μg/ml) was chosen for the pharmacodynamic studies, because the mutant prevention concentration (MPC) of linezolid against the parent strain in the presence of RM9 at 102(but not at 104) CFU/ml did not differ from the MPC value determined in the absence of the RMs. Five-day treatments with twice-daily linezolid doses were simulated at concentrations either between the MIC and MPC or above the MPC.S. aureusRMs (resistant to 2× and 4× MIC but not 8× and 16× MIC) were enriched at ratios of the 24-h area under the concentration-time curve (AUC24) to the MIC that provide linezolid concentrations between the MIC and MPC for 100% (AUC24/MIC, 60 h) and 86% (AUC24/MIC, 120 h) of the dosing interval. No such enrichment occurred when linezolid concentrations were above the MIC and below the MPC for a shorter time (37% of the dosing interval; AUC24/MIC, 240 h) or when concentrations were consistently above the MPC (AUC24/MIC, 480 h). These findings obtained using linezolid-susceptible staphylococci supplemented with RMs support the mutant selection window hypothesis. This method provides an option to delineate antibiotic concentration-resistance relationships with bacteria that exhibit low mutation frequencies.
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Guan, Weide, Shoudao Huang, Derong Luo, and Fei Rong. "A Reverse Model Predictive Control Strategy for a Modular Multilevel Converter." Energies 12, no. 2 (January 18, 2019): 297. http://dx.doi.org/10.3390/en12020297.
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In recent years, modular multilevel converters (MMCs) have developed rapidly, and are widely used in medium and high voltage applications. Model predictive control (MPC) has attracted wide attention recently, and its advantages include straightforward implementation, fast dynamic response, simple system design, and easy handling of multiple objectives. The main technical challenge of the conventional MPC for MMC is the reduction of computational complexity of the cost function without the reduction of control performance of the system. Some modified MPC scan decrease the computational complexity by evaluating the number of on-state sub-modules (SMs) rather than the number of switching states. However, the computational complexity is still too high for an MMC with a huge number of SMs. A reverse MPC (R-MPC) strategy for MMC was proposed in this paper to further reduce the computational burden by calculating the number of inserted SMs directly, based on the reverse prediction of arm voltages. Thus, the computational burden was independent of the number of SMs in the arm. The control performance of the proposed R-MPC strategy was validated by Matlab/Simulink software and a down-scaled experimental prototype.
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Serrano-Rodríguez, J. M., C. Cárceles-García, C. M. Cárceles-Rodríguez, M. L. Gabarda, J. M. Serrano-Caballero, and E. Fernández-Varón. "Susceptibility and PK/PD relationships of Staphylococcus aureus strains isolated from the milk of sheep and goats with clinical mastitis to five veterinary fluoroquinolones." Veterinary Record 180, no. 15 (February 17, 2017): 376. http://dx.doi.org/10.1136/vr.103964.
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Minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of veterinary fluoroquinolones as enrofloxacin, its metabolite ciprofloxacin, danofloxacin, difloxacin and marbofloxacin against Staphylococcus aureus strains (n=24) isolated from milk of sheep and goats affected by clinical mastitis were evaluated. The authors have used the MIC and MPC, as well as the pharmacokinetic-pharmacodynamic relationships in plasma and milk. MIC values were significantly different between drugs, unlike MPC values. Lower MIC values were obtained for danofloxacin and difloxacin, middle and higher values for enrofloxacin, ciprofloxacin and marbofloxacin. However, differences in MPC values were not found between drugs. At conventional doses, the AUC24/MIC and AUC24/MPC ratios were close to 30–80 hours and 5–30 hours, with exception of danofloxacin, in plasma and milk. The time inside the mutant selection window (TMSW) was close to 3–6 hours for enrofloxacin, ciprofloxacin and marbofloxacin, near to 8 hours for danofloxacin and 12–22 hours for difloxacin. From these data, the mutant selection window could be higher for danofloxacin and difloxacin compared with the other fluoroquinolones tested. The authors concluded that enrofloxacin and marbofloxacin, at conventional doses, could prevent the selection of bacterial subpopulations of S aureus, unlike danofloxacin and difloxacin, where higher doses could be used.
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Credito, Kim, Klaudia Kosowska-Shick, and Peter C. Appelbaum. "Mutant Prevention Concentrations of Four Carbapenems against Gram-Negative Rods." Antimicrobial Agents and Chemotherapy 54, no. 6 (March 22, 2010): 2692–95. http://dx.doi.org/10.1128/aac.00033-10.
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ABSTRACT We tested the propensities of four carbapenems to select for resistant Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii mutants by determining the mutant prevention concentrations (MPCs) for 100 clinical strains with various ß-lactam phenotypes. Among the members of the Enterobacteriaceae family and A. baumannii strains, the MPC/MIC ratios were mostly 2 to 4. In contrast, for P. aeruginosa the MPC/MIC ratios were 4 to ≥16. The MPC/MIC ratios for β-lactamase-positive K. pneumoniae and E. coli isolates were much higher (range, 4 to >16 μg/ml) than those for ß-lactamase-negative strains.
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Liang, Beibei, Nan Bai, Yun Cai, Rui Wang, Karl Drlica, and Xilin Zhao. "Mutant Prevention Concentration-Based Pharmacokinetic/Pharmacodynamic Indices as Dosing Targets for Suppressing the Enrichment of Levofloxacin-Resistant Subpopulations of Staphylococcus aureus." Antimicrobial Agents and Chemotherapy 55, no. 5 (February 22, 2011): 2409–12. http://dx.doi.org/10.1128/aac.00975-10.
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ABSTRACTMIC- and mutant prevention concentration (MPC)-based pharmacokinetic/pharmacodynamic (PK/PD) indices were compared for suitability as attainment targets for restricting amplification of levofloxacin-resistant mutant subpopulations. When threeStaphylococcus aureusstrains were examined with a hollow-fiber PK/PD model, area under the concentration-time curve over 24 h (AUC24)/MPC values of >25 and maximum concentration of drug in serum (Cmax)/MPC values of >2.2 predicted resistance outcome among different isolates with an interisolate kappa coefficient of 1. MIC-based mutant-restrictive PK/PD values varied >8-fold and exhibited only a moderate interisolate agreement (kappa coefficient of 0.5). Thus, MPC-based PK/PD indices are more suitable than MIC-based indices for predicting mutant-restricting fluoroquinolone doses when multiple bacterial isolates are considered.
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Zhanel, George G., Vibhu Vishisht, Ed Tam, Daryl J. Hoban, and James A. Karlowsky. "Mutant Prevention Concentrations of Doripenem and Meropenem Alone and in Combination with Colistin (Polymyxin E), Levofloxacin and Tobramycin inPseudomonas aeruginosa." Canadian Journal of Infectious Diseases and Medical Microbiology 20, suppl a (2009): 67A—71A. http://dx.doi.org/10.1155/2009/801612.
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BACKGROUND: With a limited number of available antimicrobial agents to treatPseudomonas aeruginosainfections, the prevention of emergence of antimicrobial resistance and its subsequent spread is critical. In the present study, the mutant prevention concentration (MPC) of doripenem was examined and compared with meropenem for its ability to prevent resistant mutant selection forP aeruginosawhen used alone and in combination with the other antipseudomonal agents colistin (polymyxin E), levofloxacin and tobramycin. OBJECTIVE: To determine if two antimicrobial agents that possessed different mechanisms of action and separate demonstrated activities againstP aeruginosawould produce a reduced MPC in combination compared with the MPC of each agent alone. METHODS: Twelve clinical isolates ofP aeruginosawere plated on Mueller-Hinton agar containing 1×, 2×, 4×, 8×, 16× and 32× the doripenem, imipenem or meropenem minimum inhibitory concentration (MIC), and also on agar containing doripenem or meropenem in combination with either tobramycin (6 μg/mL), colistin (2 μg/mL or 8 μg/mL), levofloxacin (8 μg/mL) or azithromycin (0.4 μg/mL). The MPC for each antimicrobial agent-isolate combination was defined as the lowest antibiotic concentration that prevented the visible growth of mutant colonies at 48 h of incubation. The MPC/MIC (μg/mL) ratio was defined as the ratio of the MPC obtained to the original MIC. RESULTS: The MPC/MIC ratios of doripenem alone ranged from 8 to 32 for the twelve isolates tested compared with 32 for two isolates and greater than 32 for 10 isolates with imipenem, and 32 for three isolates and greater than 32 for nine isolates with meropenem. All antimicrobials tested exhibited markedly elevated MPCs compared with their original MICs with MPC/MIC ratios of 8 to 32 for doripenem, 32 to greater than 32 for imipenem, 32 to greater than 32 for meropenem, 32 to greater than 32 for colistin (tested at 2 μg/mL), 8 to 16 for levofloxacin and 8 to 32 for tobramycin. When a second antimicrobial was used in combination with doripenem, the MPC/MIC ratio decreased up to twofold for doripenem combined with colistin (2 μg/mL), decreased four- to 16-fold for doripenem combined with colistin (8 μg/mL), decreased eight- to 32-fold for doripenem combined with levofloxacin, and decreased four- to 16-fold for doripenem combined with tobramycin. Adding a second antimicrobial in combination with meropenem resulted in the following decreases in MPC/MIC: no decrease for meropenem combined with colistin (2 μg/mL), four to greater than eightfold decrease for meropenem combined with colistin (8 μg/mL), four- to 16-fold decrease for meropenem combined with levofloxacin, and two- to 16-fold decrease for meropenem combined with tobramycin. For all antimicrobial combinations tested, doripenem yielded greater decreases in MPC/MIC ratios than did meropenem. CONCLUSION: The present study found that individual antipseudomonal antimicrobial agents tested against 12 clinical isolates ofP aeruginosahad eight- to greater than 32-fold higher MPCs than MICs, that combining doripenem or meropenem with a second active antipseudomonal agent with a different mechanism of action was more effective at preventing resistance selection than the two agents used individually, and finally, that doripenem was less likely than both imipenem and meropenem to select for spontaneous resistance mutants ofP aeruginosa.
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Shetgaonkar, Ajay, Aleksandra Lekić, José Luis Rueda Torres, and Peter Palensky. "Microsecond Enhanced Indirect Model Predictive Control for Dynamic Power Management in MMC Units." Energies 14, no. 11 (June 5, 2021): 3318. http://dx.doi.org/10.3390/en14113318.
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The multi-modular converter (MMC) technology is becoming the preferred option for the increased deployment of variable renewable energy sources (RES) into electrical power systems. MMC is known for its reliability and modularity. The fast adjustment of the MMC’s active/reactive powers, within a few milliseconds, constitutes a major research challenge. The solution to this challenge will allow accelerated integration of RES, without creating undesirable stability issues in the future power system. This paper presents a variant of model predictive control (MPC) for the grid-connected MMC. MPC is defined using a Laguerre function to reduce the computational burden. This is achieved by reducing the number of parameters of the MMC cost function. The feasibility and effectiveness of the proposed MPC is verified in the real-time digital simulations. Additionally, in this paper, a comparison between an accurate mathematical and real-time simulation (RSCAD) model of an MMC is given. The comparison is done on the level of small-signal disturbance and a Mean Absolute Error (MAE). In the MMC, active and reactive power controls, AC voltage control, output current control, and circulating current controls are implemented, both using PI and MPC controllers. The MPC’s performance is tested by the small and large disturbance in active and reactive powers, both in an offline and online simulation. In addition, a sensitivity study is performed for different variables of MPC in the offline simulation. Results obtained in the simulations show good correspondence between mathematical and real-time analytical models during the transient and steady-state conditions with low MAE. The results also indicate the superiority of the proposed MPC with the stable and fast active/reactive power support in real-time simulation.
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Koç, Atakan, and Çağrı Arı. "Milk Yield, Reproduction and Milk Quality Characteristics of Simmental and Red-Holstein Cattle Raised at a Dairy Farm in Aydın Province: 2. Milk Quality." Turkish Journal of Agriculture - Food Science and Technology 8, no. 10 (October 17, 2020): 2074–80. http://dx.doi.org/10.24925/turjaf.v8i10.2074-2080.3512.
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In this study, the milk quality characteristics of Simmental (SIM) and Red-Holstein (RH) breeds raised in a private farm in Aydın were determined. As milk quality properties, the percentages of protein (MPC), lactose (MLC), non-fat dry matter (NFDMC), total dry matter (TDMC), casein (MCC) contents and also milk urea nitrogen (MUN), oleic acid (OA), beta-hydroxybutyric acid (BHBA) and somatic cell count (SCC) were determined. The averages of MPC, MLC, NFDMC, TDMC, MCC, MUN, OA, BHBA and Log10SCC belonging to RH and SIM breeds are 3.38 ± 0.021% and 3.40 ± 0.015%, 4.86 ± 0.028% and 4.81 ± 0.019%, 9.09 ± 0.037 and 9.09 ± 0.025, 11.18 ± 0.069 and 11.23 ± 0.048, 2.50 ± 0.020 and 2.44 ± 0.014, 12.07 ± 0.200 mg / dl and 12.28 ± 0.138 mg / dl, 0.258 ± 0.0095 g / 100 g and 0.255 ± 0.0065 g / 100 g, 0.284 ± 0.138 mmol / L and 0.269 ± 0.0093 mmol / L, and 5.417 ± 0.0173 (261216 cells / ml) and 5.401 ± 0.0118 (251768 cells / ml) were found, respectively. The breed did not differ significantly in milk quality characteristics, except for MCC. The lower SCC level in milk and the suitable level of MUN for both breeds shows that the factors such as maintenance-feeding-housing-herd management in the farm were optimal in this herd.
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Gelasakis, Athanasios I., Apostolos Angelidis, Rebecca Giannakou, and Georgios Arsenos. "Bacterial subclinical mastitis and its effect on milk quality traits in low-input dairy goat herds." Veterinary Record 183, no. 14 (July 25, 2018): 449. http://dx.doi.org/10.1136/vr.104804.
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The objective of the study was to investigate and quantify the effects of subclinical mastitis (SCM) on the gross chemical composition of milk in low-input dairy goat herds. Dairy goats (n=590) of two native Greek breeds from four representative low-input farms were randomly selected and used in the study. Α prospective study was conducted, including monthly monitoring and milk sampling of the same individual goats during the course of two consecutive milking periods. Mixed linear regression models were built to assess how the chemical composition of milk was affected by (1) SCM and (2) the different pathogens isolated from SCM cases. Goats with SCM had lower milk-fat content (MFC), daily milk-fat yield (DMFY), milk-lactose content (MLC) and daily milk-lactose yield (DMLY), and slightly higher milk-protein content (MPC) and daily milk-protein yield (DMPY), compared with goats without SCM. Milk produced by goats with SCM due to coagulase-positive staphylococci and Mycoplasma agalactiae had significantly lower MFC, DMFY, MLC and DMLY, and higher MPC and DMPY, compared with the milk produced by healthy goats. Finally, goats with SCM due to coagulase-negative staphylococci had lower DMFY, MLC and DMLY and higher DMPY compared with the healthy ones.
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Lastovetsky, Alexey L. "mpC." ACM SIGPLAN Notices 31, no. 2 (February 1996): 13–20. http://dx.doi.org/10.1145/226060.226064.
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Weycker, Derek, Xiaoyan Li, Alex Kartashov, Rich Barron, John Edelsberg, Hairong Xu, Vincent Girardi, and Gary H. Lyman. "Risk and Consequences of Neutropenic Complications Among Patients with Metastatic Solid Tumors Receiving Myelosuppressive Chemotherapy." Blood 122, no. 21 (November 15, 2013): 2962. http://dx.doi.org/10.1182/blood.v122.21.2962.2962.
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Abstract Background While several studies have evaluated the risk and consequences of febrile neutropenia (FN) among patients receiving cancer chemotherapy in US clinical practice, none have focused on a broad group of patients with metastatic disease. Methods A retrospective cohort design and US healthcare claims data (2007-2011) were utilized. Study population included adult patients who underwent myelosuppressive chemotherapy for metastatic cancer of the breast (MBC), colon/rectum (MCC), lung (MLC), ovaries (MOC), or prostate (MPC). For each subject, the first qualifying chemotherapy course and each chemotherapy cycle therein, and each episode of chemotherapy-induced neutropenic complications (CINC) during the course, were identified; use of prophylaxis with colony-stimulating factors (CSF) and oral antimicrobial (AMB) agents also was identified. CINC was ascertained using broad (diagnosis of neutropenia, fever, and/or infection) and narrow (diagnosis of neutropenia) definitions, and was stratified by care setting. (Our outcome was CINC, rather than FN, because clinical data were not available and there is no specific diagnosis code for FN. In a validation study, FN risk was reported to be between risk of CINC based alternatively on aforementioned broad and narrow criteria [Weycker, BMC Health Services Research 2013].) Risk (i.e., incidence proportion) of CINC was estimated by tumor type and regimen; consequences of CINC-hospital length of stay (LOS) and mortality, CINC-related healthcare costs-were estimated by tumor type. Results CINC risk is reported herein only for the most frequently observed regimen for each tumor type: paclitaxel for MBC (17.8% of 15,309 patients), 5-fluorouracil + leucovorin + oxaliplatin for MCC (23.4% of 16,934), carboplatin + paclitaxel for MLC (22.9% of 21,994), carboplatin + paclitaxel for MOC (49.2% of 7,435), and docetaxel for MPC (68.4% of 4,668). Across these 5 regimens, use of CSF prophylaxis in cycle 1 ranged from 4.6-24.6% (Table 1). Risk of CINC (broad definition) during the course ranged from 11.6-20.5%; among subjects with CINC, 87.7-95.3% had CINC in the inpatient setting and 16.8-33.8% had CINC in cycle 1. For CINC requiring inpatient care (broad definition), hospital mortality ranged from 4.4-9.8%, hospital LOS (mean) from 6.9-7.3 days, and healthcare costs (mean) from $12,831-$16,003 across tumor types (Table 2). CINC risks based on narrow definition are in Table 1; CINC consequences based on narrow definition were similar to those for broad definition. Conclusion Among patients receiving common myelosuppressive chemotherapy regimens for metastatic disease in solid tumors in US clinical practice, 4.6-24.6% were administered CSF prophylaxis in cycle 1, while 11.6-20.5% experienced CINC (broad definition), treated most often in the inpatient setting. Disclosures: Weycker: Amgen Inc.: Research Funding. Li:Amgen Inc.: Employment, Equity Ownership. Kartashov:Amgen Inc.: Research Funding. Barron:Amgen Inc.: Employment, Equity Ownership. Edelsberg:Amgen Inc.: Research Funding. Xu:Amgen Inc.: Employment, Equity Ownership. Girardi:Amgen Inc.: Employment, Equity Ownership. Lyman:Amgen Inc.: PI on a research grant to Duke University Other.
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Golikova, Maria V., Elena N. Strukova, Kamilla N. Alieva, Vladimir A. Ageevets, Alisa A. Avdeeva, Ofeliia S. Sulian, and Stephen H. Zinner. "Meropenem MICs at Standard and High Inocula and Mutant Prevention Concentration Inter-Relations: Comparative Study with Non-Carbapenemase-Producing and OXA-48-, KPC- and NDM-Producing Klebsiella pneumoniae." Antibiotics 12, no. 5 (May 8, 2023): 872. http://dx.doi.org/10.3390/antibiotics12050872.
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The minimal inhibitory concentration (MIC) is conventionally used to define in vitro levels of susceptibility or resistance of a specific bacterial strain to an antibiotic and to predict its clinical efficacy. Along with MIC, other measures of bacteria resistance exist: the MIC determined at high bacterial inocula (MICHI) that allow the estimation of the occurrence of inoculum effect (IE) and the mutant prevention concentration, MPC. Together, MIC, MICHI and MPC represent the bacterial “resistance profile”. In this paper, we provide a comprehensive analysis of such profiles of K. pneumoniae strains that differ by meropenem susceptibility, ability to produce carbapenemases and specific carbapenemase types. In addition, we have analyzed inter-relations between the MIC, MICHI and MPC for each tested K. pneumoniae strain. Low IE probability was detected with carbapenemase-non-producing K. pneumoniae, and high IE probability was detected with those that were carbapenemase-producing. MICs did not correlate with the MPCs; significant correlation was observed between the MICHIs and the MPCs, indicating that these bacteria/antibiotic characteristics display similar resistance properties of a given bacterial strain. To determine the possible resistance-related risk due to a given K. pneumoniae strain, we propose determining the MICHI. This can more or less predict the MPC value of the particular strain.
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Bakeer, Abualkasim, Mohammed Alhasheem, and Saeed Peyghami. "Efficient Fixed-Switching Modulated Finite Control Set-Model Predictive Control Based on Artificial Neural Networks." Applied Sciences 12, no. 6 (March 18, 2022): 3134. http://dx.doi.org/10.3390/app12063134.
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The disadvantage of finite control set-model predictive control (FCS-MPC) is that the switching frequency is variable and relies on the sampling time and operating point. This paper describes how to implement a new algorithm to achieve a fixed-switching frequency functionality for the FCS-MPC. The used approach combines the FCS-MPC with the SVPWM, resulting in the calculation of dwell times and the selection of the best two active vectors for the next sample interval. These dwell times have a significant impact on FCS-MPC performance during transient and steady-state conditions, and their values are determined using various mathematical models. To solve the problem of the fixed-switching frequency with lower harmonics distortion compared to the conventional modulated MPC (M2PC), an ANN-based trained network is proposed to calculate the duty-cycle of the applied vectors and thus the dwell time in the next sampling interval. The ANN network receives the cost functions of the two active vectors and the zero vector from the M2PC control algorithm and determines the optimal duty-cycle for each vector based on a proper tuning. In this way, three goals are achieved, the first goal is that the algorithm explicitly obtains a fixed-switching frequency, and secondly, the cost is as simple as the conventional M2PC. Finally, the feature of including objectives and non-linearity is still applicable. The paper’s case study used the two level voltage source inverter (2L-VSI) for uninterruptible power supply (UPS) applications. The results based on MATLAB/Simulink revealed that the ANN-M2PC has retained all FCS-MPC features in addition to operating at a fixed-switching frequency, while the power quality is significantly enhanced.
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Dahdouh, E., S. H. Shoucair, S. E. Salem, and Z. Daoud. "Mutant Prevention Concentrations of Imipenem and Meropenem againstPseudomonas aeruginosaandAcinetobacter baumannii." Scientific World Journal 2014 (2014): 1–7. http://dx.doi.org/10.1155/2014/979648.
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The aim of this study was to determine the usefulness of the MPC of carbapenems against clinical isolates ofPseudomonasspp.andAcinetobacterspp. and to assess its possible relationship with mechanisms of resistance. Detection of the mechanisms of resistance was performed using Antibiotic Susceptibility Testing, Double Disk Synergy, disk antagonism, addition of NaCl to the medium, addition of PBA or EDTA to Carbapenem disks, addition of PBA to Cefoxitin disks, and CCCP test for 10Pseudomonasspp. andAcinetobacter baumanniistrains. The MIC and MPC were determined using the broth macrodilution and plate dilution methods, respectively. FourAcinetobacter baumanniistrains produced MBL. Two of them produced Oxacillinase and one produced ESBL. TwoPseudomonasspp. isolates produced both KPC and MBL. The resistantAcinetobacterspp. andPseudomonasspp. strains had higher MPC values than susceptible ones. However, the Mutant Selection Window was found to be dependent on the degree of resistance but not on a particular mechanism of resistance. The usefulness of the MPC was found to be dependent on its value. Based on our data, we recommend determining the MPC for each isolate before using it during treatment. Furthermore, the use of T>MSW instead of T>MIC is suggested.
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Homma, Tomoyuki, Toshihiko Hori, Giichi Sugimori, and Yoshinori Yamano. "Pharmacodynamic Assessment Based on Mutant Prevention Concentrations of Fluoroquinolones To Prevent the Emergence of Resistant Mutants of Streptococcus pneumoniae." Antimicrobial Agents and Chemotherapy 51, no. 11 (July 30, 2007): 3810–15. http://dx.doi.org/10.1128/aac.01372-06.
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ABSTRACT The objective of this study was to investigate the relationship between pharmacokinetic and pharmacodynamic parameters, on the basis of the mutant prevention concentration (MPC) concept, and the emergence of resistant mutants of Streptococcus pneumoniae to fluoroquinolone antibacterials. Some clinical isolates with various MIC and MPC values of moxifloxacin and levofloxacin were exposed under conditions simulating the time-concentration curves observed when moxifloxacin (400 or 80 mg, once a day) or levofloxacin (200 mg, twice a day) was orally administered by using an in vitro pharmacodynamic model. The decrease in susceptibility was evaluated by altering the population analysis profiles after moxifloxacin or levofloxacin treatment for 72 h. When the area under the concentration-time curve from 0 to 24 h (AUC0-24)/MPC and peak concentration (C max)/MPC were above 13.41 and 1.20, respectively, complete eradication occurred and no decrease in susceptibility was observed. On the other hand, when AUC0-24/MPC and C max/MPC were below 0.84 and 0.08, respectively, the susceptibility decreased. However, the time inside the mutant selective window and the time above the MPC did not show any correlation with the decrease in susceptibility. These results suggest that AUC0-24/MPC and C max/MPC are important parameters for predicting the emergence of resistant mutants and that higher values indicate greater effectiveness.
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Reid, Suzanna, Alec Ritchie, Landin Boring, Jennifa Gosling, Scott Cooper, Giao Hangoc, Israel F. Charo, and Hal E. Broxmeyer. "Enhanced Myeloid Progenitor Cell Cycling and Apoptosis in Mice Lacking the Chemokine Receptor, CCR2." Blood 93, no. 5 (March 1, 1999): 1524–33. http://dx.doi.org/10.1182/blood.v93.5.1524.
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Abstract Chemokines regulate hematopoiesis in part by influencing the proliferative status of myeloid progenitor cells (MPC). Human MCP-1/murine JE, a myelosuppressive chemokine, specifically binds C-C chemokine receptor 2 (CCR2). Transgenic mice containing a targeted disruption in CCR2 that prevents expression of CCR2 mRNA and protein and have MPC that are insensitive to inhibition by MCP-1 and JE in vitro were assessed for potential abnormalities in growth of bone marrow (BM) and spleen MPC. MPC in both unseparated and c-kit+lin− populations of BM from CCR2-deficient (−/−) mice were in a greatly increased proliferation state compared with CCR2 littermate control (+/+) mice, an effect not apparent with progenitors from spleens of CCR2 (−/−) mice. Increased cycling status of CCR2 (−/−) BM MPC did not result in increased numbers of nucleated cells or MPC in BM or spleens of CCR2 (−/−) mice. Possible reasons for this apparent discrepancy were highlighted by flow cytometric analysis of c-kit+lin− BM cells and colony formation by MPC subjected to delayed addition of growth factors. The c-kit+lin− population of BM cells from CCR2 (−/−) mice had a significantly higher percentage of apoptotic cells than those from CCR2 (+/+) BM. However, elevated apoptosis was not associated with decreased numbers of c-kit+lin− cells. The increased percentage of apoptotic c-kit+lin− cells was due to elevated apoptosis within the c-kitdimlin−, but not the c-kitbrightlin−, subpopulations of cells. Consistent with enhanced apoptosis of phenotypically defined cells, MPC from CCR2 (−/−) BM and purified c-kit+lin− cells demonstrated decreased cell survival in vitro upon delayed addition of growth factors. The data suggest that signals received by CCR2 limit proliferation of progenitor cells in the BM, but also enhance survival of these cells.
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Reid, Suzanna, Alec Ritchie, Landin Boring, Jennifa Gosling, Scott Cooper, Giao Hangoc, Israel F. Charo, and Hal E. Broxmeyer. "Enhanced Myeloid Progenitor Cell Cycling and Apoptosis in Mice Lacking the Chemokine Receptor, CCR2." Blood 93, no. 5 (March 1, 1999): 1524–33. http://dx.doi.org/10.1182/blood.v93.5.1524.405k07_1524_1533.
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Chemokines regulate hematopoiesis in part by influencing the proliferative status of myeloid progenitor cells (MPC). Human MCP-1/murine JE, a myelosuppressive chemokine, specifically binds C-C chemokine receptor 2 (CCR2). Transgenic mice containing a targeted disruption in CCR2 that prevents expression of CCR2 mRNA and protein and have MPC that are insensitive to inhibition by MCP-1 and JE in vitro were assessed for potential abnormalities in growth of bone marrow (BM) and spleen MPC. MPC in both unseparated and c-kit+lin− populations of BM from CCR2-deficient (−/−) mice were in a greatly increased proliferation state compared with CCR2 littermate control (+/+) mice, an effect not apparent with progenitors from spleens of CCR2 (−/−) mice. Increased cycling status of CCR2 (−/−) BM MPC did not result in increased numbers of nucleated cells or MPC in BM or spleens of CCR2 (−/−) mice. Possible reasons for this apparent discrepancy were highlighted by flow cytometric analysis of c-kit+lin− BM cells and colony formation by MPC subjected to delayed addition of growth factors. The c-kit+lin− population of BM cells from CCR2 (−/−) mice had a significantly higher percentage of apoptotic cells than those from CCR2 (+/+) BM. However, elevated apoptosis was not associated with decreased numbers of c-kit+lin− cells. The increased percentage of apoptotic c-kit+lin− cells was due to elevated apoptosis within the c-kitdimlin−, but not the c-kitbrightlin−, subpopulations of cells. Consistent with enhanced apoptosis of phenotypically defined cells, MPC from CCR2 (−/−) BM and purified c-kit+lin− cells demonstrated decreased cell survival in vitro upon delayed addition of growth factors. The data suggest that signals received by CCR2 limit proliferation of progenitor cells in the BM, but also enhance survival of these cells.
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Soomro, Jahangeer Badar, Faheem Akhtar Chachar, Madad Ali Shah, Abdul Aziz Memon, Faisal Alsaif, and Sager Alsulamy. "Optimized Circulating Current Control and Enhanced AC Fault Ride-through Capability Using Model Predictive Control for MMC-HVDC Applications." Energies 16, no. 13 (July 4, 2023): 5159. http://dx.doi.org/10.3390/en16135159.
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This paper presents a novel model predictive control (MPC) approach for suppressing circulating currents in MMC-based HVDC systems. The proposed MPC eliminates the need for PI-regulators and pulse width modulators, resulting in improved dynamic response and controllability. The methodology demonstrates exceptional efficacy in controlling output current and addressing voltage ripple concerns associated with sub module (SM) capacitors. An innovative, communication-free fault ride-through (FRT) method is also introduced, eliminating the need for a DC chopper and ensuring rapid recovery following faults. To overcome the computational challenges associated with the traditional MPC algorithm, an aggregate model of the MMC is proposed, significantly reducing predicted states, hardware requirements, and calculations. Simulations validate the robustness of the proposed MPC control algorithm in tracking AC side current, suppressing circulating current, and regulating capacitor voltages under various scenarios. Future research will explore system expansion, integration with renewable energy sources, and hardware-in-loop setup testing for further validation.
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Alotaibi, Abdullah, Jerrold Petrofsky, Noha S. Daher, Everett Lohman, Hasan M. Syed, and Haneul Lee. "The Effect of Monophasic Pulsed Current with Stretching Exercise on the Heel Pain and Plantar Fascia Thickness in Plantar Fasciitis: A Randomized Controlled Trial." Healthcare 8, no. 2 (March 30, 2020): 79. http://dx.doi.org/10.3390/healthcare8020079.
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Plantar fasciitis (PF) is one of the most common causes of heel and foot pain. Monophasic pulsed current (MPC) is an electrical stimulation used to accelerate the healing processes. The purpose of this study was to determine the effect of MPC and MPC combined with plantar fascia stretching exercises (SE) on heel pain and plantar fascia thickness in treatment of PF and see if there is any relationship between heel pain and plantar fascia thickness after intervention. Forty-four participants diagnosed with PF were randomly assigned to two group; MPC group or MPC combined with plantar fascia SE. Plantar fascia thickness was measured with musculoskeletal ultrasound. Although no statistical differences between the two groups were found, heel pain and the plantar fascia thickness significantly decreased in both groups after the intervention (p < 0.001). No significant correlation was found between changes in heel pain and plantar fascia thickness after 4 weeks of treatment. Our results indicated that MPC can reduce heel pain and plantar fascia thickness caused by PF. However, MPC combined with plantar fascia SE is not superior to MCP only in terms of reduction in heel pain and plantar fascia thickening.
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Hermsen, Elizabeth D., Laurie B. Hovde, George N. Konstantinides, and John C. Rotschafer. "Mutant Prevention Concentrations of ABT-492, Levofloxacin, Moxifloxacin, and Gatifloxacin against Three Common Respiratory Pathogens." Antimicrobial Agents and Chemotherapy 49, no. 4 (April 2005): 1633–35. http://dx.doi.org/10.1128/aac.49.4.1633-1635.2005.
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ABSTRACT The purpose of this study was to compare the mutant prevention concentration (MPC) of ABT-492 to those of levofloxacin, moxifloxacin, and gatifloxacin against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The fluoroquinolones had comparable mutation selection windows, which is the ratio of MPC/MIC, for all isolates.
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Chen, Yongxin, Jonathan Gelfond, Linda M. McManus, and Paula K. Shireman. "Temporal microRNA expression during in vitro myogenic progenitor cell proliferation and differentiation: regulation of proliferation by miR-682." Physiological Genomics 43, no. 10 (May 2011): 621–30. http://dx.doi.org/10.1152/physiolgenomics.00136.2010.
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MicroRNAs (miRNAs) regulate gene expression by repressing target genes at the posttranscriptional level. Since miRNAs have unique expression profiles in different tissues, they provide pivotal regulation of many biological processes. The present study defined miRNA expression during murine myogenic progenitor cell (MPC) proliferation and differentiation to identify miRNAs involved in muscle regeneration. Muscle-related gene expression analyses revealed that the time course and expression of myosin heavy chain (MHC) and transcription factors (Myf5, MyoD, myogenin, and Pax7) were similar during in vitro MPC proliferation/differentiation and in vivo muscle regeneration. Comprehensive profiling revealed that 139 or 16 miRNAs were significantly changed more than twofold [false discovery rate (FDR) < 0.05] during MPC differentiation or proliferation, respectively; cluster analyses revealed five distinct patterns of miRNA expression during the time course of MPC differentiation. Not unexpectedly, the largest miRNA changes occurred in muscle-specific miRNAs (miR-1, -133a, and -499), which were upregulated >10-fold during MPC differentiation (FDR < 0.01). However, several previously unreported miRNAs were differentially expressed, including miR-10b, -335-3p, and -682. Interestingly, the temporal patterns of miR-1, -499, and -682 expression during in vitro MPC proliferation/differentiation were remarkably similar to those observed during in vivo muscle regeneration. Moreover, in vitro inhibition of miR-682, the only miRNA upregulated in proliferating compared with quiescent MPC, led to decreased MPC proliferation, further validating our in vitro assay system for the identification of miRNAs involved in muscle regeneration. Thus the differentially expressed miRNAs identified in the present study could represent new regulatory elements in MPC proliferation and differentiation.
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Wahid, Abdul, and Naufal Syafiq Maro. "Multi Input Multi Output (MIMO) Control 2x2 at Vacuum Distillation Unit for LVGO, MVGO, and HVGO Production." E3S Web of Conferences 67 (2018): 03012. http://dx.doi.org/10.1051/e3sconf/20186703012.
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Currently, Indonesia is still experiencing a fuel deficit, so it is necessary to build a new oil refinery and a process optimization at an existing refinery. A vacuum distillation unit (VDU) is used to process the atmospheric residue products from crude distillation unit (CDU). A multivariable model predictive control (MMPC) is proposed to improve a control performance in VDU because of the interaction between variables in the unit. Therefore, it is necessary to find the variables that interact with each other. In this study only two variables are discussed. Set point (SP) and disturbance changes are used to test the control performance with integral of square error (ISE) as the indicator. The results are compared with the control performance of the PI controller and a single MPC. As a result, the feed flow rate and bottom-stage temperature are strongest interactions so that both are determined as controlled variables in MMPC. The control performance of MMPC is better than the PI controller and the single MPC with control performance improvement of 48% to the PI controller and 21% to MPC on for Feed Flow Rates, and 98% to the PI controller and 27% to MPC on Bottom Stage Temperature. While on disturbance changes the enhancement is 35% for the Bottom Stage Temperature.
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Zhang, Jiayuan, Mengyuan Wu, Shuo Diao, Shixing Zhu, Chu Song, Jiali Yue, Frederico S. Martins, et al. "Pharmacokinetic/Pharmacodynamic Evaluation of Aztreonam/Amoxicillin/Clavulanate Combination against New Delhi Metallo-β-Lactamase and Serine-β-Lactamase Co-Producing Escherichia coli and Klebsiella pneumoniae." Pharmaceutics 15, no. 1 (January 11, 2023): 251. http://dx.doi.org/10.3390/pharmaceutics15010251.
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This study aimed to examine specific niches and usage for the aztreonam/amoxicillin/clavulanate combination and to use population pharmacokinetic simulations of clinical dosing regimens to predict the impact of this combination on restricting mutant selection. The in vitro susceptibility of 19 New-Delhi metallo-β-lactamase (NDM)-producing clinical isolates to amoxicillin/clavulanate and aztreonam alone and in co-administration was determined based on the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC). The fractions of a 24-h duration that the free drug concentration was within the mutant selection window (fTMSW) and above the MPC (fT>MPC) in both plasma and epithelial lining fluid were determined from simulations of 10,000 subject profiles based on regimens by renal function categories. This combination reduced the MIC of aztreonam and amoxicillin/clavulanate to values below their clinical breakpoint in 7/9 K. pneumoniae and 8/9 E. coli, depending on the β-lactamase genes detected in the isolate. In the majority of the tested isolates, the combination resulted in fT>MPC > 90% and fTMSW < 10% for both aztreonam and amoxicillin/clavulanate. Clinical dosing regimens of aztreonam and amoxicillin/clavulanate were sufficient to provide mutant restriction coverage for MPC and MIC ≤ 4 mg/L. This combination has limited coverage against NDM- and extended-spectrum β-lactamase co-producing E. coli and K. pneumoniae and is not effective against isolates carrying plasmid-mediated AmpC and KPC-2. This study offers a potential scope and limitations as to where the aztreonam/amoxicillin/clavulanate combination may succeed or fail.
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GUAN, JIAN-GUO, JUN HUANG, SU-LING ZHAO, and RUN-ZHANG YUAN. "CHARACTERIZATION AND PROPERTIES OF METAL PHTHALOCYANINE-Fe3O4 NANOCOMPOSITES FOR ELECTROMAGNETORHEOLOGICAL FLUIDS." International Journal of Modern Physics B 15, no. 06n07 (March 20, 2001): 599–609. http://dx.doi.org/10.1142/s0217979201005052.
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Meso-scale metal phthalocyanine (MPc, M=Cu, Ni, Mn, or Co)- Fe 3 O 4 nanocomposites for EMR fluids have been prepared and well characterized. The results indicate that there exists chemical bonding between MPc and Fe 3 O 4 nanoparticles, and their strength of chemical bonding increases in the following order: NiPc < CuPc < CoPc ~ MnPc . Compared to Fe 3 O 4 nanoparticles, MPc- Fe 3 O 4 nanocomposites have superior ability to anti-oxidation and thermal stability, and show almost the same saturation magnetic strength, but much less coercive force. All MPc- Fe 3 O 4 nanocomposites have irregular spherical shape with D of 0.2~0.4 μ m . The EMR fluids containing MPc- Fe 3 O 4 nanocomposites in chlorinated paraffin oil have excellent stability and redispersibilty. They show reversible significant field-induced shear stress, which increase linearly with the increment of electric field strength (E) or H and which are different for MPc- Fe 3 O 4 nanocomposites containing various metal elements, when E or H is applied respectively. Furthermore, field-induced shear stress shows obvious synergetic effect when E and H are applied simultaneously.
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Botrus, Gehan, Denise Roe, Gayle S. Jameson, Pedro Luiz Serrano Uson Junior, Ronald Lee Korn, Lana Caldwell, Taylor Bargenquast, Max Miller, and Erkut Hasan Borazanci. "Mitomycin C in Homologous Recombination Deficient Metastatic Pancreatic Cancer after Disease Progression on Platinum-Based Chemotherapy and Olaparib." Biomedicines 10, no. 11 (October 26, 2022): 2705. http://dx.doi.org/10.3390/biomedicines10112705.
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Recent efforts to personalize treatment with platinum-based chemotherapy and PARP inhibitors have produced promising results in homologous recombinant deficient (HRD) metastatic pancreatic cancer (MPC). However, new strategies are necessary to overcome resistance. The below case series documents patients treated at the HonorHealth Research Institute with a diagnosis of HRD MPC who received Mitomycin C (MMC) treatment from January 2013 until July 2018. Five HRD MPC patients treated with MMC were evaluated. All patients received at least one course of treatment. Mean age at MMC treatment initiation was 58 years. There were 3 females and 2 males. All patients had tumors that progressed on platinum-based chemotherapy, four patients had previous exposure to Olaparib. The median PFS was 10.1 months, and the median OS was 12.3 months. Responses were observed only in patients harboring BRCA2 mutations, no response was observed in the PALB2 mutation carrier. MMC in this heavily previously treated PC was safe, with overall manageable grade 2 gastrointestinal toxicities including nausea and vomiting, and G3 hematological toxicities including anemia and thrombocytopenia. Pancreatic cancer patients with HRD may benefit from MMC treatment. Further clinical investigation of MMC in pancreatic cancer is warranted.
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Sluis, Geerte L. Van, Paris Margaritis, Michael Sliozberg, Jenna Mauer, Armida Faella, Shangzhen Zhou, Katherine A. High, Arnold Spek, and Valder R. Arruda. "Zymogen Protein C as a Novel Modulator of Cancer Progression In Murine Models." Blood 116, no. 21 (November 19, 2010): 718. http://dx.doi.org/10.1182/blood.v116.21.718.718.
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Abstract Abstract 718 Recent evidence on the role of the protein C (PC) pathway in tumor progression of the experimental mouse melanoma model has revealed that inhibition of the cytoprotective effects of endogenous activated PC (aPC) enhances tumor cell extravasation, whereas exogenous administration of recombinant human APC has a protective effect. Moreover transgenic mice overexpressing endothelial PC receptor (EPCR) in tissue endothelium exhibit low rates of tumor metastasis. Here we report our findings in C57Bl/6 mice expressing murine forms of APC or zymogen PC by viral-mediated gene transfer. Vector-injected mice resulted in continuous expression of murine APC (mAPC) or PC (mPC), which reached plateau levels after week 2. On week 3, we administered B16F10 murine melanoma cells (3.5×10^5) intravascularly and analyzed the rates of lung metastasis 21 days later compared to age and gender matched saline-injected groups (control cohort=26 mice). We observed a dose-dependent protective effect of mAPC. Mice expressing mAPC at levels of 7.3 ± 1.5 ng/ml (n=8) or lower (determined by a functional ELISA-capture assay) did not differ from saline injected mice (that had baseline mAPC levels < 3 ng/ml). By increasing the vector dose, mAPC levels of 25.6 ± 4.8 ng/ml (n=16) to 118 ±6 ng/ml (n=10) reduced the numbers of lung metastasis compared to saline injected mice (p<0.05). To investigate the contribution of the cytoprotective/anticoagulant role of mAPC, we injected mice with a variant form of mAPC with reduced anticoagulant but intact cytoprotective activity (mAPC-5A). Following melanoma cell infusion, animals expressing levels of mAPC-5A ranging from 15.2 ± 3.2 ng/ml (n=16) to 80.4 ± 4.7 ng/ml (n=10) exhibited rates of lung metastasis similar to controls. To further explore the anticoagulant pathway in this metastasis model, we injected mice with AAV expressing zymogen mPC. There was a dose-dependent increase in the mPC levels measured by a chromogenic assay resulting in 3–4 fold of normal levels. However, this was not associated with increased levels of mAPC compared to saline-injected mice. Notably, in the mPC expressing mice (n=26), the rates of tumor metastasis were significantly reduced compared to controls (p<0.005). The protective effect of zymogen mPC remained even in the absence of protease-activated receptor (PAR-1), one main cellular receptor for the APC-mediated cytoprotective effect. In particular, the lung metastasis rates in PAR-1 null mice expressing mPC (n=21) were lower than PAR-1 null mice injected with saline (n=15) (p<0.01). Lastly, the hemostatic effects of the expressed transgenes (mPC, mAPC and mAPC-5A) in all mice were investigated. Prolongation of the activated partial prothrombin time and increase blood loss following tail clipping assay was restricted to animals expressing APC-WT in a dose-dependent manner but not in APC-5A or zymogen PC compared to controls. These findings support a novel and important role of zymogen PC in modulating tumor progression with minimal risk of bleeding. Disclosures: High: Genzyme, Inc: Consultancy, Patents & Royalties; Third Rock Ventures: Consultancy; PTC Therapeutics:; Amsterdam Molecular Therapeutics:; Sangamo Biosciences:; Novo-Nordisk: Consultancy; Shire, Inc.: Consultancy.
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Kesteman, Anne-Sylvie, Aude A. Ferran, Agnès Perrin-Guyomard, Michel Laurentie, Pascal Sanders, Pierre-Louis Toutain, and Alain Bousquet-Mélou. "Influence of Inoculum Size and Marbofloxacin Plasma Exposure on the Amplification of Resistant Subpopulations of Klebsiella pneumoniae in a Rat Lung Infection Model." Antimicrobial Agents and Chemotherapy 53, no. 11 (September 8, 2009): 4740–48. http://dx.doi.org/10.1128/aac.00608-09.
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ABSTRACT We tested the hypothesis that the bacterial load at the infection site could impact considerably on the pharmacokinetic/pharmacodynamic (PK/PD) parameters of fluoroquinolones. Using a rat lung infection model, we measured the influence of different marbofloxacin dosage regimens on selection of resistant bacteria after infection with a low (105 CFU) or a high (109 CFU) inoculum of Klebsiella pneumoniae. For daily fractionated doses of marbofloxacin, prevention of resistance occurred for an area-under-the-concentration-time-curve (AUC)/MIC ratio of 189 h for the low inoculum, whereas for the high inoculum, resistant-subpopulation enrichment occurred for AUC/MIC ratios up to 756 h. For the high-inoculum-infected rats, the AUC/MIC ratio, C max/MIC ratio, and time within the mutant selection window (T MSW) were not found to be effective predictors of resistance prevention upon comparison of fractionated and single administrations. An index corresponding to the ratio of the time that the drug concentrations were above the mutant prevention concentration (MPC) over the time that the drug concentrations were within the MSW (T > MPC/T MSW) was the best predictor of the emergence of resistance: a T > MPC/T MSW ratio of 0.54 was associated with prevention of resistance for both fractionated and single administrations. These results suggest that the enrichment of resistant bacteria depends heavily on the inoculum size at the start of an antimicrobial treatment and that classical PK/PD parameters cannot adequately describe the impact of different dosage regimens on enrichment of resistant bacteria. We propose an original index, the T > MPC/T MSW ratio, which reflects the ratio of the time that the less susceptible bacterial subpopulation is killed over the time that it is selected, as a potentially powerful indicator of prevention of enrichment of resistant bacteria. This ratio is valid only if plasma concentrations achieve the MPC.
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Prous, J., and J. Castañer. "MPC-1304." Drugs of the Future 16, no. 1 (1991): 25. http://dx.doi.org/10.1358/dof.1991.016.01.129877.
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McIntyre, J. A., J. Castañer, and D. Fernández-Forner. "MPC-7869." Drugs of the Future 31, no. 1 (2006): 22. http://dx.doi.org/10.1358/dof.2006.031.01.961798.
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Sindelar, Georg, Xilin Zhao, Anthony Liew, Yuzhi Dong, Tao Lu, Jianfeng Zhou, John Domagala, and Karl Drlica. "Mutant Prevention Concentration as a Measure of Fluoroquinolone Potency against Mycobacteria." Antimicrobial Agents and Chemotherapy 44, no. 12 (December 1, 2000): 3337–43. http://dx.doi.org/10.1128/aac.44.12.3337-3343.2000.
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ABSTRACT Mutant prevention concentration (MPC) has been proposed as a new measure of antibiotic potency by which the ability to restrict selection of resistant mutants is evaluated. To determine whether MPC provides potency information unavailable from the more customary measurement of the MIC, 18 fluoroquinolones were examined for their ability to block the growth of Mycobacterium smegmatis and to select resistant mutants from wild-type populations. Both MPC and MIC were affected by changes in the moiety at the fluoroquinolone C-8 position and in alkyl groups attached to the C-7 piperazinyl ring. When eight resistant mutants, altered in the gyrase A protein, were tested with fluoroquinolones having either a methoxy or a hydrogen at the C-8 position, the MIC for the most resistant mutant correlated better with the MPC than did the MIC for wild-type cells. For C-8-fluorine derivatives, which were generally less active than the C-8-methoxy compounds but which were more active than C-8-hydrogen derivatives, the MICs for both the mutant and the wild type correlated well with the MPCs. Thus, measurement of the MICs for wild-type cells can reflect the ability of a quinolone to restrict the selection of resistance, but often it does not. With the present series of compounds, the most potent contained a C-8-methoxy and a small group attached to the C-7 ring.
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Weihua, Zhao, and Tiauw Hiong Go. "Robust Decentralized Formation Flight Control." International Journal of Aerospace Engineering 2011 (2011): 1–13. http://dx.doi.org/10.1155/2011/157590.
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Motivated by the idea of multiplexed model predictive control (MMPC), this paper introduces a new framework for unmanned aerial vehicles (UAVs) formation flight and coordination. Formulated using MMPC approach, the whole centralized formation flight system is considered as a linear periodic system with control inputs of each UAV subsystem as its periodic inputs. Divided into decentralized subsystems, the whole formation flight system is guaranteed stable if proper terminal cost and terminal constraints are added to each decentralized MPC formulation of the UAV subsystem. The decentralized robust MPC formulation for each UAV subsystem with bounded input disturbances and model uncertainties is also presented. Furthermore, an obstacle avoidance control scheme for any shape and size of obstacles, including the nonapriorily known ones, is integrated under the unified MPC framework. The results from simulations demonstrate that the proposed framework can successfully achieve robust collision-free formation flights.
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Zhao, Xilin, William Eisner, Nathan Perl-Rosenthal, Barry Kreiswirth, and Karl Drlica. "Mutant Prevention Concentration of Garenoxacin (BMS-284756) for Ciprofloxacin-Susceptible or -Resistant Staphylococcus aureus." Antimicrobial Agents and Chemotherapy 47, no. 3 (March 2003): 1023–27. http://dx.doi.org/10.1128/aac.47.3.1023-1027.2003.
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ABSTRACT The new quinolone garenoxacin (BMS-284756), which lacks a C-6 fluorine, was examined for its ability to block the growth of Staphylococcus aureus. Measurement of the MIC and the mutant prevention concentration (MPC) revealed that garenoxacin was 20-fold more potent than ciprofloxacin for a variety of ciprofloxacin-susceptible isolates, some of which were resistant to methicillin. The MPC for 90% of the isolates (MPC90) was below published serum drug concentrations achieved with recommended doses of garenoxacin. These in vitro observations suggest that garenoxacin has a low propensity for selective enrichment of fluoroquinolone-resistant mutants among ciprofloxacin-susceptible isolates of S. aureus. For ciprofloxacin-resistant isolates, the MIC at which 90% of the isolates tested were inhibited was below serum drug concentrations while the MPC90 was not. Thus, for these strains, garenoxacin concentrations are expected to fall inside the mutant selection window (between the MIC and the MPC) for much of the treatment time. As a result, garenoxacin is expected to selectively enrich mutants with even lower susceptibility.
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Petrovskaya, Tatyana A., and Dmitry V. Tapalskiy. "Influence of different antibiotic groups on the development of mutational resistance to colistin among Klebsiella pneumoniae." Clinical Microbiology and Antimicrobial Chemotherapy 23, no. 2 (2021): 166–72. http://dx.doi.org/10.36488/cmac.2021.2.166-172.
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Objective. To determine the concentration of colistin, preventing the selection of colistin-resistant mutants of K. pneumoniae, and to evaluate the effect of antibiotics of different groups on the development of mutational resistance to colistin. Materials and Methods. Minimum inhibitory concentrations (MIC) of colistin were determined for 88 K. pneumoniae strains by the method of serial microdilutions in broth, and carbapenemase genes were detected. The selection of colistin-resistant subpopulations was performed on cation-adjusted MüllerHinton agar (MHA) with the addition of 16 mg/l colistin. Mutant prevention concentration (MPC) of colistin is determined on MHA containing 0, 1, 2, 4, 8, 16, 32, 64 and 128 mg/l of colistin. Also, MPCs of colistin were determined in the presence of a fixed concentration of the second antibiotic: clarithromycin (2 mg/l), azithromycin (2 mg/l), rifampicin (1 mg/l), clindamycin (0.5 mg/l), meropenem (8 mg/l), linezolid (2 mg/l), amikacin (1 mg/l), vancomycin (2 mg/l), doxycycline (2 mg/l). Results. All strains remained susceptible to colistin (colistin MIC 0.06–1.0 mg/l). Resistance to meropenem (MIC > 8 mg/l) was detected in 48 strains (54.5%), 46 of them were carbapenemase producers: KPC – 6 strains (6.8%), OXA-48 – 26 strains (29.5%), NDM – 14 strains (15.9%). Growth of colonies on MHA with 16 mg/l of colistin was found for 96.6% of the strains. The frequency of mutational resistance occurrence ranged from 6 × 10-9 to 10-6 (median: 2 × 10-7). The mutational nature of colistin resistance was confirmed for 36.4% of the strains. The MPC values of colistin were in the range of 16–256 mg/l; (MPC50 32 mg/l, MPC90 256 mg/l) and significantly (32–1024 times) exceeded the MIC values. In the presence of 1 mg/l of rifampicin, the MPC of colistin decreased 4–64 times (MPC50 4 mg/l, MPC90 4 mg/l). In the presence of 2 mg/l of doxycycline, MPC of colistin decreased 2–64 times for all strains (MPC50 8 mg/l, MPC90 16 mg/l). The presence of linezolid (2 mg/l) and vancomycin (2 mg/l) did not significantly change MPC of colistin. Meropenem at a concentration of 8 mg/l had no significant effect on colistin MPC for carbapenemase-producing K. pneumoniae strains. None of the antibiotics lowered the MPC50 of colistin to its clinically achievable serum concentrations. Conclusions. A high frequency of formation of mutational resistance to colistin in K. pneumoniae was revealed. The MPC values of colistin are outside the range of clinically achievable serum concentrations and may decrease in the presence of other antibiotics.
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Saltarelli, Francesca, Alessandro Moscetti, Guglielmo Bruno, Bruno Monarca, Gerardo Salerno, Maria Teresa Corsetti, Patrizia Cardelli, Giovanna Ferranti, and Giacinto La Verde. "Heart Function In Systemic and Localized AL Amyloidosis: Role of NT-ProBNP and MPC-1." Blood 116, no. 21 (November 19, 2010): 5006. http://dx.doi.org/10.1182/blood.v116.21.5006.5006.
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Abstract Abstract 5006 In AL amyloidosis typical sites of amyloid buildup are heart, skin, gastrointestinal tract, liver, kidneys, and blood vessels. To evaluate the heart involvement in systemic and localized amyloidosis proBNP, peptide (NT-proBNP; 76 amino acids) and MPC-1 were investigated. NT-proBNP have been described as useful marker for the diagnosis heart disease, and its plasma concentrations correlate with the functional classification of patients according to the New York Heart Association (NYHA). MCP-1 is a chemokine that activates mononuclear phagocytes by promoting leukocyte–endothelium binding and migration to sites of inflammation. The MCP-1 levels seem to be related to the severity of cardiac alteration, as demonstrated by the coronary angiogram. NT-proBNP and MPC-1 serum levels were performed in systemic or localized AL amyloidosis to evaluate if there was a difference in the heart involvement. Blood samples were collected from 8 patients with systemic amyloidosis and from 4 patients with localized amyloidosis. To analyze the results of NT-proBNP and MPC-1, Mann-Whitney test was performed. NT-proBNP serum values were significantly (p=0.007) increased in systemic disease. Also, MPC-1 serum levels were significantly (p=0.004) higher in the patients with systemic disease (350.52±58.70 pg/ml) if compared to the group of localized amyloidosis (147.82±26.03 pg/ml). On the basis of our results, the heart seem to be functionally more involved in AL systemic amyloidosis than in localized disease, as demonstrated by the higher NT-proBNP and MPC-1 serum values. Disclosures: No relevant conflicts of interest to declare.
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Chang, Kuo-Wei, Chia-En Lin, Hsi-Feng Tu, Hsin-Yao Chung, Yi-Fen Chen, and Shu-Chun Lin. "Establishment of a p53 Null Murine Oral Carcinoma Cell Line and the Identification of Genetic Alterations Associated with This Carcinoma." International Journal of Molecular Sciences 21, no. 24 (December 8, 2020): 9354. http://dx.doi.org/10.3390/ijms21249354.
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Head and neck squamous cell carcinoma (HNSCC), including oral squamous cell carcinoma (OSCC), ranks sixth in cancer incidence worldwide. To generate OSCC cells lines from human or murine tumors, greatly facilitates investigations into OSCC. This study describes the establishing of a mouse palatal carcinoma cell line (designated MPC-1) from a spontaneous tumor present in a heterozygous p53 gene loss C57BL/6 mouse. A MPC-1-GFP cell subclone was then generated by lentivirus infection resulting in stable expression of green fluorescent protein. Assays indicated that MPC-1 was a p53 null polygonal cell that was positive for keratinocyte markers; it also expressed vimentin and showed a loss of E-cadherin expression. Despite that MPC-1 having strong proliferation and colony formation capabilities, the potential for anchorage independent growth and tumorigenesis was almost absent. Like other murine MOC-L and MTCQ cell line series we have previously established, MPC-1 also expresses a range of stemness markers, various oncogenic proteins, and a number of immune checkpoint proteins at high levels. However, the synergistic effects of the CDK4/6 inhibitor palbociclib on other therapeutic drugs were not observed with MPC-1. Whole exon sequencing revealed that there were high rates of non-synonymous mutations in MPC-1 affecting various genes, including Akap9, Arap2, Cdh11, Hjurp, Mroh2a, Muc4, Muc6, Sp110, and Sp140, which are similar to that the mutations present in a panel of chemical carcinogenesis-related murine tongue carcinoma cell lines. Analysis has highlighted the dis-regulation of Akap9, Cdh11, Muc4, Sp110, and Sp140 in human HNSCC as indicated by the TCGA and GEO OSCC databases. Sp140 expression has also been associated with patient survival. This study describes the establishment and characterization of the MPC-1 cell line and this new cell model should help to advance genetic research into oral cancer.
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Uckun, F., S. Morar, J. Larson, and S. Qazi. "Survival outcome of metastatic adenocarcinoma patients after patient-tailored outpatient chemotherapy guided by fusion imaging." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 13145. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.13145.
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13145 Background: We treated 173 patients with metastatic Stage IV adenocarcinoma, including 65 patients with metastatic colorectal cancer (MCRC), 22 patients with metastatic pancreas cancer (MPC), and 86 patients with metastatic breast cancer (MBC) in an outpatient setting. The metastatic sites included liver (49% of patients), bone (39%), lung (36%), brain (16%), peritoneum (16%), lymph node (14%) and chest wall (8%). Methods: MCRC patients received multiple cycles of Xeloda-based empirical chemotherapy regimens: alone or in combination with Irinotecan, Oxaliplatin or Mitomycin. MPC patients were given cycles of Gemcitabine-based empirical chemotherapy regimens: alone or with Cisplatin, 5-FU or Xeloda. MBC patients received cycles of Taxol-based chemotherapy: alone or with Adriamycin, Carboplatin or Gemcitabine; Xeloda plus Taxotere or Vinorelbine; Gemcitabine plus Taxotere or Vinorelbine; and Adriamycin plus Taxotere. Anatomic imaging/fusion technology with combined anatomic and functional imaging (CT/MRI fused with whole body PET scans) plus serial cancer marker level measurements monitored response to therapy and in patients showing evidence of progression on a given regimen were switched to a different treatment regimen. Results: Kaplan Meier calculated median survival time for all 173 metastatic adenocarcinoma patients was 17 mo (95% CI 13–19 mo); for subgroups medians were 12 mo (9–16 mo), 16 (8–22 mo) and 22 mo (18–42 mo) for MCRC, MPC and MBC patients respectively. The probability of living at 1 yr after initiation of therapy was 61 ± 6% for all patients, 47 ± 6% for MCRC, 59 ± 10% for MPC and 72 ± 5% for MBC patients. Our results indicate that a significant portion of previously treated patients with MCRC, MPC and MBC with liver, lung, and/or brain metastases can achieve objective responses and long-term progression-free survival with an excellent quality of life on patient tailored outpatient treatments guided by fusion imaging. Conclusions: Fusion technology provides a powerful diagnostic tool for timely termination or modification of ineffective treatments. Empirical patient-tailored chemotherapy should be offered to metastatic adenocarcinoma patients as an alternative to the clinical trial and hospice options. No significant financial relationships to disclose.
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Hamedelniel Suliman, Munzir, Mohammad Nahid Siddiqui, and Chanbasha Basheer. "Surface Functionalization of Mesoporous Carbon for the Enhanced Removal of Strontium and Cesium Radionuclides." Coatings 10, no. 10 (September 25, 2020): 923. http://dx.doi.org/10.3390/coatings10100923.
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Mesoporous carbons (MPC) and modified mesoporous carbons (MMPC) were prepared from asphalt for the adsorption of several metal ions from the aqueous solution. In this study, we investigated the adsorption efficiency of Cesium (Cs+) and Strontium (Sr2+) ions using mesoporous and modified mesoporous carbons. The optimum conditions for the removal of Cs+ and Sr2+ were at 10.0 pH, 1.00 ppm (1000.0 µg/L) concentration, 20.0 min contact time, 0.20 g/L adsorbent dose, 25.0 °C temperature with more than 95.0% removal of Cs+ and Sr2+ ions using MMPC. The limit of detection (LOD) was found to be 0.030 ppb and 10.00 ppb for Sr2+ and Cs+ metals ions, respectively, while the Limit of quantification (LOQ) was calculated to be 0.10 ppb for Sr2+ and 35.00 ppb for Cs+ metals ions. The functionalization of the MPC was performed using potassium permanganate to get MMPC, which were characterized by FT-IR spectroscopy. The nature of the X-ray diffraction peaks suggests that the MPC and MMPC carbons are amorphous and semi-crystalline materials. The scanning electron microscope (SEM) and transition electron microscope (TEM) studies showed the changes in the morphology due to the adsorption on the surface of the carbons. The TEM analysis clearly showed that the metal ions blocked most of the pores on the surface. The surface area, by N2 adsorption isotherm (BET), of MPC and MMPC were 937 and 667 m2·g−1, respectively. Among the adsorption isotherms, Langmuir isotherm showed the best linearity. The Langmuir isotherm indicates that the adsorption is monolayer and homogeneous with a finite number of ions. Adsorption kinetics showed better linearity with pseudo-second-order plots and obeys this order. This process indicates that the chemical interaction, such as covalent or ionic bonding, took place between the metal ions and the carbon adsorbents.
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Разиньков, Egor Razinkov, Воропаев, O. Voropaev, Киев, and N. Kiev. "THE DEFINITION OF THE LIMIT OF SATURATION WITH WOOD PLATES FOR DOMESTIC PREMISES." Forestry Engineering Journal 7, no. 1 (August 15, 2017): 162–67. http://dx.doi.org/10.12737/25207.
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One of the topical issues of the application of furniture in domestic premises is defining its limiting (maximum) saturation in the premises so that the air in these premises, the allocation of harmful substances does not exceed the maximum allowable level (maximum permissible concentrations - MPC). It is known that in using furniture of wood-based panels (particle Board, Chipboard, wood fiber, MDF) this substance is formaldehyde. Currently, the MoH established the formaldehyde MPC in the air at the level of 0.01 mg/m3. The aim of this work was to determine the limit of saturation with the wood plates in premises, provided that indoor formaldehyde emissions from plates will not exceed the established by the Ministry of health MPC. This definition of the limit of saturation (Ls, m2 of plates/m3 of the premises air) was performed according to our previously derived formula. Calculations were made for furniture (cabinet furniture, tables, beds of panel design, furniture for sitting and lying, beds with soft headboards and elements), floor coverings and wall panels. In the result, it was found that, for example, when using chipboard of E1 formaldehyde emission class in designs of furniture, tables, beds of panel construction value of Ls when the IISP is 1.0 m2/m3 of air (saturation of the volume of air with plates in their testing by chamber method) and MPC=0.01 mg/m3 is 4.03 m2 /room, and when MPC=0.124 mg/m3 (adopted by the countries-participants of the WTO and the World Health Organization) it will make 50.05 m2/room. When using plates of the same emission class, and for the same value of IISP, when MPC=0.01 mg/m3 Ls value is 6.25 m2 /room, when MPC=0.124 mg/m3 it will make 77.63 m2 /room. When using E1 class chipboard panels in the construction of furniture for sitting and lying, beds with soft headboards and elements, Ls value in the IISP is equal to 0.3 m2/m3 air and at MPC=0.01 mg/m3 is of 1.21 m2 /room, and when MPC=0.124 mg/m3 it will make 15.02 m2/room. When using plates of the same emission class, and for the same value of IISP at Mac=0.01 mg/m3 Ls value is 1.88 m2/room, when MPC=0.124 mg/m3 it will make 23.45 m2/room.
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Chi, Hengxuan, and Karl R. Englund. "Interfacial properties of magnesium phosphate ceramics and sugar maple (Acer saccharum)." Holzforschung 68, no. 5 (July 1, 2014): 575–82. http://dx.doi.org/10.1515/hf-2013-0113.
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Abstract The interfacial shear strength (τi) between magnesium phosphate ceramics (MPC) and sugar maple (Acer saccharum) has been evaluated by means of a pullout test method. The binder system monopotassium phosphate (MKP) and magnesium oxide (MgO) resulted in the highest τi at a MKP/MgO ratio of 3:1. The influence of the levels of MPC binder and aggregates on the interfacial properties has been observed based on a mixture design model. The aggregates were Portland cement (PC), wollastonite (WO), and vitrified calcium aluminosilicates (VCAS). The MPC binder level was the primary factor influencing τi, while WO and VCAS can mutually promote τi. However, τi is decreased when PC is mixed with the two other aggregates. The environmental durability of VCAS-based MPC (V-MPC), PC-based MPC (C-MPC), and WO-based MPC (W-MPC) was assessed by treatments at conditioning (90% relative humidity) and water immersion. The V-MPC/maple has very poor moisture performance, while the C-MPC/maple and W-MPC/maple had reduced interfacial shear stresses but still maintained bond integrity unlike the V-MPC.
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Wu, Fan, Mario Eduardo Villanueva, and Boris Houska. "Ambiguity tube MPC." Automatica 146 (December 2022): 110648. http://dx.doi.org/10.1016/j.automatica.2022.110648.
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Granado, Ernesto, William Colmenares, Jacques Bernussou, and Germain Garcia. "LMI BASED MPC." IFAC Proceedings Volumes 35, no. 1 (2002): 177–82. http://dx.doi.org/10.3182/20020721-6-es-1901.00598.
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Heirung, Tor Aksel N., B. Erik Ydstie, and Bjarne Foss. "Towards Dual MPC." IFAC Proceedings Volumes 45, no. 17 (2012): 502–7. http://dx.doi.org/10.3182/20120823-5-nl-3013.00070.
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Lopes de Lima, Marcelo, Eduardo Camponogara, Daniel Limon Marruedo, and David Munoz de la Pena. "Distributed Satisficing MPC." IEEE Transactions on Control Systems Technology 23, no. 1 (January 2015): 305–12. http://dx.doi.org/10.1109/tcst.2014.2312395.
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Almashaqbeh, Ghada, Fabrice Benhamouda, Seungwook Han, Daniel Jaroslawicz, Tal Malkin, Alex Nicita, Tal Rabin, Abhishek Shah, and Eran Tromer. "Gage MPC: Bypassing Residual Function Leakage for Non-Interactive MPC." Proceedings on Privacy Enhancing Technologies 2021, no. 4 (July 23, 2021): 528–48. http://dx.doi.org/10.2478/popets-2021-0083.
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Abstract Existing models for non-interactive MPC cannot provide full privacy for inputs, because they inherently leak the residual function (i.e., the output of the function on the honest parties’ input together with all possible values of the adversarial inputs). For example, in any non-interactive sealed-bid auction, the last bidder can figure out what was the highest previous bid. We present a new MPC model which avoids this privacy leak. To achieve this, we utilize a blockchain in a novel way, incorporating smart contracts and arbitrary parties that can be incentivized to perform computation (“bounty hunters,” akin to miners). Security is maintained under a monetary assumption about the parties: an honest party can temporarily supply a recoverable collateral of value higher than the computational cost an adversary can expend. We thus construct non-interactive MPC protocols with strong security guarantees (full security, no residual leakage) in the short term. Over time, as the adversary can invest more and more computational resources, the security guarantee decays. Thus, our model, which we call Gage MPC, is suitable for secure computation with limited-time secrecy, such as auctions. A key ingredient in our protocols is a primitive we call “Gage Time Capsules” (GaTC): a time capsule that allows a party to commit to a value that others are able to reveal but only at a designated computational cost. A GaTC allows a party to commit to a value together with a monetary collateral. If the original party properly opens the GaTC, it can recover the collateral. Otherwise, the collateral is used to incentivize bounty hunters to open the GaTC. This primitive is used to ensure completion of Gage MPC protocols on the desired inputs. As a requisite tool (of independent interest), we present a generalization of garbled circuit that are more robust: they can tolerate exposure of extra input labels. This is in contrast to Yao’s garbled circuits, whose secrecy breaks down if even a single extra label is exposed. Finally, we present a proof-of-concept implementation of a special case of our construction, yielding an auction functionality over an Ethereum-like blockchain.
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Zanon, Mario, Sébastien Gros, and Moritz Diehl. "Indefinite linear MPC and approximated economic MPC for nonlinear systems." Journal of Process Control 24, no. 8 (August 2014): 1273–81. http://dx.doi.org/10.1016/j.jprocont.2014.04.023.
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Temmerman, Robin, An Garmyn, Gunther Antonissen, Gerty Vanantwerpen, Mia Vanrobaeys, Freddy Haesebrouck, and Mathias Devreese. "Evaluation of Fluoroquinolone Resistance in Clinical Avian Pathogenic Escherichia coli Isolates from Flanders (Belgium)." Antibiotics 9, no. 11 (November 12, 2020): 800. http://dx.doi.org/10.3390/antibiotics9110800.
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Fluoroquinolones are frequently used antimicrobials for the treatment of avian pathogenic Escherichia coli (APEC) infections. However, rapid development and selection of resistance to this class of antimicrobial drugs is a significant problem. The aim of this study was to investigate the occurrence and mechanisms of antimicrobial resistance against enrofloxacin (ENRO) in APEC strains in Flanders, Belgium. One hundred and twenty-five APEC strains from broilers with clinical colibacillosis were collected in Flanders from November 2017 to June 2018. The minimum inhibitory concentration (MIC) of all strains and the mutant prevention concentration (MPC) of a sample of sensitive isolates were determined using a commercial gradient strip test and via the agar dilution method, respectively. Non-wild type (NWT) isolates were further characterized using polymerase chain reaction (PCR), gel electrophoresis and gene sequencing. Forty percent of the APEC strains were NWT according to the epidemiological cut-off (ECOFF) measure (MIC > 0.125 μg/mL). With respect to clinical breakpoints, 21% were clinically intermediate (0.5 ≤ MIC ≤ 1 μg/mL) and 10% were clinically resistant (MIC ≥ 2). The MPC values of the tested strains ranged from 0.064 to 1 μg/mL, resulting in MPC/MIC ratios varying from 4 to 32. The majority (92%) of the NWT strains carried one or two mutations in gyrA. Less than a quarter (22%) manifested amino acid substitutions in the topoisomerase IV parC subunit. Only three of the NWT strains carried a mutation in parE. Plasmid mediated quinolone resistance (PMQR) associated genes were detected in 18% of the NWT strains. In contrast to the relatively large number of NWT strains, only a small percentage of APEC isolates was considered clinically resistant. The most common MPC value for sensitive strains was 0.125 μg/mL. Some isolates showed higher values, producing wide mutant selection windows (MSW). Chromosomal mutations in DNA gyrase and topoisomerase IV were confirmed as the main source of decreased antimicrobial fluoroquinolone susceptibility, de-emphasizing the role of PMQR mechanisms.
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Chan, Alex H., Randall F. D'Souza, Joseph W. Beals, Nina Zeng, Utpal Prodhan, Aaron C. Fanning, Sally D. Poppitt, et al. "The Degree of Aminoacidemia after Dairy Protein Ingestion Does Not Modulate the Postexercise Anabolic Response in Young Men: A Randomized Controlled Trial." Journal of Nutrition 149, no. 9 (June 1, 2019): 1511–22. http://dx.doi.org/10.1093/jn/nxz099.
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ABSTRACT Background Resistance exercise and dietary protein stimulate muscle protein synthesis (MPS). The rate at which proteins are digested and absorbed into circulation alters peak plasma amino acid concentrations and may modulate postexercise MPS. A novel mineral modified milk protein concentrate (mMPC), with identical amino acid composition to standard milk protein concentrate (MPC), was formulated to induce rapid aminoacidemia. Objectives The aim of this study was to determine whether rapid aminoacidemia and greater peak essential amino acid (EAA) concentrations induced by mMPC would stimulate greater postresistance exercise MPS, anabolic signaling, and ribosome biogenesis compared to standard dairy proteins, which induce a small but sustained plasma essential aminoacidemia. Methods Thirty healthy young men (22.5 ± 3.0 y; BMI 23.8 ± 2.7 kg/m2) received primed constant infusions of l-[ring-13C6]-phenylalanine and completed 3 sets of leg presses and leg extensions at 80% of 1 repetition. Afterwards, participants were randomly assigned in a double-blind fashion to consume 25 g mMPC, MPC, or calcium caseinate (CAS). Vastus lateralis biopsies were collected at rest, and 2 and 4 h post exercise. Results Plasma EAA concentrations, including leucine, were 19.2–26.6% greater in the mMPC group 45–90 min post ingestion than in MPC and CAS groups (P < 0.001). Myofibrillar fractional synthetic rate from baseline to 4 h was increased by 82.6 ± 64.8%, 137.8 ± 72.1%, and 140.6 ± 52.4% in the MPC, mMPC, and CAS groups, respectively, with no difference between groups (P = 0.548). Phosphorylation of anabolic signaling targets (P70S6KThr389, P70S6KThr421/Ser424, RPS6Ser235/236, RPS6Ser240/244, P90RSKSer380, 4EBP1) were elevated by <3-fold at both 2 and 4 h post exercise in all groups (P < 0.05). Conclusions The amplitude of plasma leucine and EAA concentrations does not modulate the anabolic response to resistance exercise after ingestion of 25 g dairy protein in young men. This trial was registered at http://www.anzctr.org.au/ as ACTRN12617000393358.